In-vitro comparison of a 1st and a 2nd generation US contrast agent for reflux diagnosis

Purpose: Contrast-enhanced sonographic reflux diagnosis, i.e. voiding urosonography (VUS), is gradually becoming an alternative for diagnostic imaging of vesicoureteric reflux (VUR). A limiting factor for the widespread application of VUS is the cost of the US contrast agents. The development of new US contrast agents and the possibility of reducing the administered dose are expected to lower the cost. The aim of this study was an in-vitro comparison of the new US contrast agent (SonoVue(R)), and the routinely used contrast agent Levovist(R), while taking into consideration the physical-chemical properties relevant for reflux diagnosis. Materials and Methods: The in-vitro experiment setup simulated the in-vivo VUS. The US modalities fundamental and harmonic imaging (THI/ECI, Sonoline Elegra(R), Siemens) were utilized, the latter with both low and high mechanical indices (MI). SonoVue(R) was tested in concentrations of 0.25 %, 0.5 % and 1 % and Levovist(R) at 5 % volume. The in-vitro contrast duration served as the parameter for comparison. This was defined as the time from the start of the experiment until the time when more than 50% of the image area was free of microbubbles. Results: The use of different concentrations of SonoVue(R) did not have any impact on the contrast duration. The contrast duration of SonoVue(R) turned out to be significantly longer when the US modality was switched from low to high MI. In the case of THI with high MI as is routinely with Levovist(R), the contrast duration of Levovist(R) at a concentration of 5 % was 1.1 min, whereas that of SonoVue(R) at a concentration of 1 % reached 7.3 min. This means that despite SonoVue(R) being administered at a dose five times lower than that of Levovist(R), the in-vitro contrast duration increased by more than 80%. Moreover, a freshly prepared suspension of SonoVue(R) did not show change in the contrast duration for nearly 6 hours. In the case of Levovis(R) there was a significant reduction in the contrast duration after only a half hour. Conclusion: The in-vivo use of SonoVue is expected to yield a significant dose reduction so that one vial can be used for more than one examination. A measurable cost reduction can consequently be achieved.